| First Author | Crnčec I | Year | 2018 |
| Journal | Mol Oncol | Volume | 12 |
| Issue | 4 | Pages | 514-528 |
| PubMed ID | 29419930 | Mgi Jnum | J:320558 |
| Mgi Id | MGI:6873865 | Doi | 10.1002/1878-0261.12178 |
| Citation | Crncec I, et al. (2018) STAT1 is a sex-specific tumor suppressor in colitis-associated colorectal cancer. Mol Oncol 12(4):514-528 |
| abstractText | The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1(IEC) ). Male but not female STAT1(IEC) mice were more resistant to DSS-induced colitis than sex-matched STAT1(flox/flox) controls and displayed reduced intraepithelial infiltration of CD8(+) TCRalphabeta(+) granzyme B(+) T cells. Moreover, DSS treatment failed to induce expression of T-cell-attracting chemokines in intestinal epithelial cells of male but not of female STAT1(IEC) mice. Application of the AOM-DSS protocol for induction of colitis-associated CRC resulted in increased intestinal tumor load in male but not in female STAT1(IEC) mice. A sex-specific stratification of human CRC patients corroborated the data obtained in mice and revealed that reduced tumor cell-intrinsic nuclear STAT1 protein expression is a poor prognostic factor in men but not in women. These data demonstrate that epithelial STAT1 is a male-specific tumor suppressor in CRC of mice and humans. |
